Posterior Pituitary Hormones PDF

Lecture 4 Dep. of Medical Physiology Dr.HananAltaee Objectives:  Define the role of the hypothalamus in producing and secreting hormones of the posterior pituitary....

Lecture 4 Dep. of Medical Physiology Dr.HananAltaee Objectives:  Define the role of the hypothalamus in producing and secreting hormones of the posterior pituitary.  Discuss the effects of vasopressin, the receptors on which it acts, and how its secretion is regulated.  Discuss the effects of oxytocin, the receptors on which it acts, and how its secretion is regulated. Posterior Pituitary Gland and its Relation to the Hypothalamus The posterior pituitary gland, also called the neurohypophysis, is composed mainly of glial-like cells called pituicytes. The pituicytes do not secrete hormones; they act simply as a supporting structure for large numbers of terminal nerve fibers and terminal nerve endings from nerve tracts that originate in the supraoptic and paraventricular nuclei of the hypothalamus (Figure 1). Figure 1: hypothalamic- hypophyseal relationship. These tracts pass to the neurohypophysis through the pituitary stalk (hypophysial stalk). The nerve endings are bulbous knobs that contain many secretory granules. These endings lie on the surfaces of capillaries, where they secrete two posterior pituitary hormones: 1. Antidiuretic hormone (ADH), also called vasopressin. 2. Oxytocin. If the pituitary stalk is cut above the pituitary gland but the entire hypothalamus is left intact, the posterior pituitary hormones continue to be secreted normally, after a transient decrease for a few days; they are then secreted by the cut ends of the fibers within the hypothalamus and not by the nerve endings in the posterior pituitary. The reason for this is that the hormones are initially synthesized in the cell bodies of the supraoptic and paraventricular nuclei and are then transported in combination with “carrier” proteins called neurophysins down to the nerve endings in the posterior pituitary gland, requiring several days to reach the gland. ADH is formed primarily in the supraoptic nuclei, whereas oxytocin is formed primarily in the paraventricular nuclei. Each of these nuclei can synthesize about one sixth as much of the second hormone as of its primary hormone. When nerve impulses are transmitted downward along the fibers from the supraoptic or paraventricular nuclei, the hormone is immediately released from the secretory granules in the nerve endings by exocytosis and is absorbed into adjacent capillaries. Both the neurophysin and the hormone are secreted together, but they are loosely bound , so the hormone separates almost immediately. The neurophysin has no known function after leaving the nerve terminals. Chemical Structures of Antidiuretic Hormone and Oxytocin Both oxytocin and ADH (vasopressin) are polypeptides, each containing nine amino acids. Their amino acid sequences are the following: Vasopressin: Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-GlyNH2 Oxytocin: Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-GlyNH2 Note that these two hormones are almost identical except that in vasopressin, phenylalanine and arginine replace isoleucine and leucine of the oxytocin molecule. The similarity of the molecules explains their partial functional similarities. In addition, vasopressin and oxytocin are synthesized in the gonads and the adrenal cortex, and oxytocin is present in the thymus. The functions of the peptides in these organs are unsettled. Physiological Functions OF Antidiuretic Hormone: The injection of extremely minute quantities of ADH— as small as 2 nanograms—can cause decreased excretion of water by the kidneys (antidiuresis). In the absence of ADH, the collecting tubules and ducts become almost impermeable to water, which prevents significant reabsorption of water and therefore allows extreme loss of water into the urine, also causing extreme dilution of the urine. Conversely, in the presence of ADH, the permeability of the collecting ducts and tubules to water increases greatly and allows most of the water to be reabsorbed as the tubular fluid passes  through these ducts, thereby conserving water in the body and producing very concentrated urine. The luminal membranes of the tubular epithelial cells of the collecting ducts are almost have a large number of special vesicles that have highly water-permeable pores called aquaporins. When ADH acts on the cell, it first combines with membrane receptors that activate adenyly cyclase and cause phosphorylation of elements of aquaporins , which then causes the vesicles to be inserted into the apical cell membranes, thus providing many areas of high water permeability. All this occurs within 5 to 10 minutes. This process temporarily provides many new pores that allow free diffusion of water from the tubular fluid through the tubular epithelial cells and into the renal interstitial fluid. Water is then absorbed from the collecting tubules and ducts by osmosis. Regulation of Antidiuretic Hormone production:  Increased Extracellular Fluid Osmolarity Stimulates ADH Secretion. When a concentrated electrolyte solution is injected into the artery that supplies the Dehydration hypothalamus, the ADH neurons in the supraoptic and paraventricular nuclei immediately transmit impulses into the posterior pituitary to release large quantities of ADH into the circulating blood, sometimes increasing the ADH secretion to as high as 20 times normal. Injection of a dilute solution into this artery causes cessation of the impulses and Overhydration therefore almost total cessation of ADH secretion. Thus, the concentration of ADH in the body fluids can change from small amounts to large amounts, or vice versa, in only a few minutes. A feedback control system is available to control the total osmotic pressure of the body fluids. Somewhere in or near the hypothalamus are modified neuron receptors called osmoreceptors, they are very sensitive to any change in Osmolarity.  When the extracellular fluid becomes too concentrated, they initiate appropriate nerve signals in the hypothalamus to cause additional ADH secretion.  Conversely, when the extracellular fluid becomes too dilute they decrease the signal for ADH secretion.(figure 2)  Figure 2: regulation of ADH secretion.  Low Blood Volume and Low Blood Pressure Stimulate ADH Secretion (Vasoconstrictor Effects of ADH).  Minute concentrations of ADH cause increased water conservation by the kidneys.  Higher concentrations of ADH have a potent effect of constricting the arterioles  For this reason, ADH has another name, vasopressin.  One of the stimuli for causing intense ADH secretion is decreased blood volume.  This occurs strongly when the blood volume decreases 15 to 25 percent or more.  The secretory rate then sometimes rises to as high as 50 times normal. The cause of this effect is the following:  The atria have stretch receptors that are excited by overfilling.  When excited, they send signals to the brain to inhibit ADH secretion.  Conversely, when the receptors are unexcited as a result of underfilling, the opposite occurs, with greatly increased ADH secretion.  Decreased stretch of the baroreceptors of the carotid, aortic, and pulmonary regions also stimulates ADH secretion. Lack of ADH–Results in diabetes insipidus Kidneys with diminished ability to conserve water Symptoms include:–Polyuria –Polydipsia Excessive levels of ADH results in Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) The syndrome causes the body to retain water and certain levels of electrolytes in the blood to fall (such as sodium). https://emedicine.medscape.com/article/246650-overview?form=fpf Oxytocin: Oxytocin is secreted mainly by paraventricular nucleus of hypothalamus. It is also secreted by supraoptic nucleus in small quantity and it is transported from hypothalamus to posterior pituitary through the nerve fibers of hypothalamo-hypophyseal tract. In the posterior pituitary, the oxytocin is stored in the nerve endings of hypothalamo- hypophyseal tract. When suitable stimuli reach the posterior pituitary from hypothalamus, oxytocin is released into the blood. Physiological Functions of Oxytocin: Oxytocin is a polypeptide having 9 amino acids. It has a half-life of about 6 minutes. It acts through activating G-protein coupled oxytocin receptor. It’s secreted in both males and females. Actions in Females Oxytocin acts on mammary glands & uterus. Action of oxytocin on mammary glands  Oxytocin causes ejection of milk from the mammary glands.  Oxytocin causes contraction of the myoepithelial cells and flow of milk from alveoli of mammary glands to the exterior through duct system and nipple.  The process by which the milk is ejected from alveoli of mammary glands is called milk ejection reflex or milk letdown reflex. It is one of the neuroendocrine reflexes. (Figure 3).  Figure 3 Milk ejection reflex. Action on uterus On pregnant uterus Throughout the period of pregnancy, oxytocin secretion is inhibited by estrogen and progesterone. At the end of pregnancy, the secretion of these two hormones decreases suddenly and the secretion of oxytocin increases. Oxytocin causes contraction of uterus and helps in the expulsion of fetus. During the later stages of pregnancy, the number of receptors for oxytocin increases in the wall of the uterus which becomes more sensitive to oxytocin. At the onset of labor, the cervix dilates and the fetus descends through the birth canal. During the movement of fetus through cervix, the receptors on the cervix are stimulated and start discharging large number of impulses. These impulses are carried to the paraventricular and supraoptic nuclei of hypothalamus by the somatic afferent nerve fibers & large quantity of oxytocin will be released, which enhances labor by causing contraction of uterus and expulsion of the fetus. The contraction of uterus during labor is also a neuroendocrine reflex. On non-pregnant uterus The action of oxytocin on non-pregnant uterus is to facilitate the transport of sperms through female genital tract up to the fallopian tube, by producing the uterine contraction during sexual intercourse. During the sexual intercourse, the receptors in the vagina are stimulated. Vaginal receptors generate the impulses, which are transmitted by somatic afferent nerves to the paraventricular and supraoptic nuclei of hypothalamus. When, these two nuclei are stimulated, oxytocin is released and transported by blood. While reaching the female genital tract, the hormone causes antiperistaltic contractions of uterus towards the fallopian tube. It is also a neuroendocrine reflex. Action in Males In males, the release of oxytocin increases during ejaculation. It facilitates release of sperm into urethra by causing contraction of smooth muscle fibers in reproductive tract, particularly vas deferens. Summary:  Neural connections run between the hypothalamus and the posterior lobe of the pituitary gland.  The hormones secreted by the posterior pituitary gland are vasopressin and oxytocin.  Vasopressin increases the permeability of the collecting ducts of the kidney to water, thus concentrating the urine.  Oxytocin acts on the breasts (lactation) and the uterus (contraction). State if the following statements about oxytocin is true or false: Oxytocin is originally synthesized in the hypothalamus. Oxytocin receptors in the target cells are in their nucleus. Oxytocin is secreted by the anterior pituitary gland. Oxytocin prolongs labour. Oxytocin's main function is to increase the rate of intestinal emptying